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© Research
Publication : Development (Cambridge, England)

Distinct levels of Notch activity for commitment and terminal differentiation of stem cells in the adult fly intestine

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Development (Cambridge, England) - 28 Sep 2011

Perdigoto CN, Schweisguth F, Bardin AJ

Link to Pubmed [PMID] – 21965616

Development 2011 Nov;138(21):4585-95

Tight regulation of self-renewal and differentiation of adult stem cells ensures that tissues are properly maintained. In the Drosophila intestine, both commitment, i.e. exit from self-renewal, and terminal differentiation are controlled by Notch signaling. Here, we show that distinct requirements for Notch activity exist: commitment requires high Notch activity, whereas terminal differentiation can occur with lower Notch activity. We identified the gene GDP-mannose 4,6-dehydratase (Gmd), a modulator of Notch signaling, as being required for commitment but dispensable for terminal differentiation. Gmd loss resulted in aberrant, self-renewing stem cell divisions that generated extra ISC-like cells defective in Notch reporter activation, as well as wild-type-like cell divisions that produced properly terminally differentiated cells. Lowering Notch signaling using additional genetic means, we provided further evidence that commitment has a higher Notch signaling requirement than terminal differentiation. Our work suggests that a commitment requirement for high-level Notch activity safeguards the stem cells from loss through differentiation, revealing a novel role for the importance of Notch signaling levels in this system.

http://www.ncbi.nlm.nih.gov/pubmed/21965616